The proposed research will examine the hypothesis that membrane alterations are prominent factors in the irreversible sickling of read blood cells. Extensions of the hypothesis are: a) lipid mobility is diminished in irreversibly sickled cells (ISCs) relative to both reversibly sickled cells (RSCs) and normal red blood cells (RBCs); b) the erythrocytic membrane microstructure is affected by sicklying resulting in altered membrane-associated cholesterol and/or phospholipid-protein and protein-protein interactions; c) differences exist in the interactions between hemoglobin (Hb) and membranes in ICSs versus RSCs or RBCs. The main goal is to investigate the nature of membrane structural and dynamic interactions relevant to red cell sickling using 1H, 31P, 13C, and 14N NMR spectra of phospholipids and hemoglobin in intact erythrocytes from patients both homozygous and heteozygous for HbS and from individuals with normal hemoglobin. A second goal is to investigate gross difference in the spectral features of intact ceils for correlation with the known clinical behavior and widely accepted fundamental concepts. A third goal is to measure the amount of polymerized HbS in various density fractions of RBCs from patients homozygous and heterozygous for HbS and HbC.